Dissociation-related behaviors in mice emerge from the inhibition of retrosplenial cortex parvalbumin interneurons.
Yue Hu, Yifan Feng, Huoqing Luo, Xiao-Na Zhu, Siyu Chen, Kexin Yang, Ziqing Deng, Mengqiang Luo, Wenjie Du, Qi Wang, Shubai Wang, Kai Wei, Ji Hu, Yingwei Wang
Cell Reports January 28, 2025 DOI: 10.1016/j.celrep.2024.115086 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | Ketamine optogenetic inhibition of RSC PV-INs |
| Topics | Ketamine |
| Keywords | Cp: neuroscience Dissociation Parvalbumin interneurons Phase-amplitude coupling Retrosplenial cortex Dissociative disorders Brain research Psychopharmacology Mental health |
| Citations | 6 |
| Key findings | Ketamine inhibits retrosplenial cortex parvalbumin interneurons, enhancing delta oscillations and delta-gamma phase-amplitude coupling, which drives dissociation-like behaviors in mice; NR1 and HCN1 in these neurons are identified as ketamine targets that may cooperatively affect dissociation. |
Abstract
Dissociation, characterized by altered consciousness and perception, underlies multiple mental disorders, but the specific neuronal subtypes involved remain elusive. In mice, we find that dissociation-inducing doses of ketamine significantly inhibit retrosplenial cortex (RSC) parvalbumin interneurons (PV-INs), enhancing delta oscillations (1-3 Hz) and delta-gamma phase-amplitude coupling (δ-γ PAC) and inducing dissociation-like behaviors. Optogenetic inhibition of RSC PV-INs triggers delta oscillations, δ-γ PAC, and some dissociation-like behaviors without ketamine. Furthermore, activation of RSC PV-INs or knockdown of the N-methyl-D-aspartate receptor subunit NR1 and the hyperpolarization-activated cyclic nucleotide-gated channel 1 (HCN1) in RSC PV-INs attenuates ketamine-induced delta oscillations, δ-γ PAC, and certain dissociation-like behaviors. These findings reveal that PV-INs regulate delta oscillations and δ-γ PAC and identify NR1 and HCN1 as ketamine targets in PV-INs that may cooperatively affect dissociation, possibly providing potential therapeutic targets for dissociative symptoms.